Ethnically Diverse iPSC-Cardiomyocyte Panel for Pharmacogenomics and Drug Safety Testing
用于药物基因组学和药物安全性测试的种族多样化 iPSC-心肌细胞小组
基本信息
- 批准号:10755624
- 负责人:
- 金额:$ 129.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-05 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAfrican American populationAgeAmerican Heart AssociationAnthracyclineAntineoplastic ProtocolsAreaArrhythmiaBiological SciencesBiotechnologyBreast Cancer TreatmentCalciumCardiacCardiac MyocytesCardiotoxicityCardiovascular AgentsCardiovascular systemCaucasiansCell LineCell SurvivalCellsCharacteristicsClientClinicalClinical TrialsCoculture TechniquesCollaborationsCollectionCommunitiesComputational BiologyCryopreservationDNA DamageDataDedicationsDevelopmentDiseaseDoseDoxorubicinDrug IndustryDrug ScreeningDrug toxicityEast AsianEconomicsElectrophysiology (science)EnsureEthnic OriginEthnic PopulationEvaluationFailureGene ExpressionGeneticGenomicsGrantHealth PersonnelHeart AbnormalitiesHispanic PopulationsHourHumanImageIndividualInvestmentsKaryotype determination procedureLaboratoriesLibrariesMalignant NeoplasmsMarketingMedicalMetabolicMetabolismModelingMorbidity - disease ratePatientsPatternPersonsPharmaceutical PreparationsPharmacogenomicsPharmacologic SubstancePharmacotherapyPharmacy (field)PopulationPopulation GeneticsPopulation HeterogeneityPredispositionProductionProtocols documentationQuantitative Trait LociReactive Oxygen SpeciesReportingResearchResearch PersonnelResourcesRiskSafetySamplingSarcomeresSmall Business Innovation Research GrantSouth AsianTechnologyTestingTimeToxicity TestsTranscription Initiation SiteTranslatingWomanWorkcell typechemotherapeutic agentcostdosagedrug candidatedrug developmentdrug discoverydrug efficacyethnic diversitygenome sequencinggenome-widehigh riskin vitro Modelindividual variationinduced pluripotent stem cellinduced pluripotent stem cell derived cardiomyocytesinter-individual variationinterestmedication safetymenmortalitymulti-electrode arraysmultiple omicsnovel therapeuticspatient populationpatient retentionpatient stratificationprecision medicinepredictive modelingprofessorresponders and non-respondersresponsesafety testingscale upscreeningsexside effectsingle-cell RNA sequencingtooltranscriptomicswhole genome
项目摘要
PROJECT SUMMARY
Cardiotoxicity is a leading cause of early and late-stage drug attrition during pharmaceutical development. The
FDA now mandates that all new drugs be tested for cardiotoxicity before entering clinical trials. However, there
needs to be a safety screening platform that can swiftly detect cardiotoxicity cost-effectively, even before
investing too much time and resource in a drug development pipeline. This is further complicated by genomic
susceptibility in the population and how they respond to drugs. A tool that can incorporate the influences of sex,
ethnicity, and genetic background can provide accurate data on the safety and efficacy of drugs and stratify
patient populations to identify responders versus non-responders. In this SBIR grant, we propose to mitigate this
issue by providing pharmacogenomics and precision medicine platforms using human induced pluripotent stem
cell-derived cardiomyocytes (iPSC-CMs). Our product is a kit comprising 100 unique and ethnically diverse iPSC
lines with equal sex representation. We aim to develop and validate this tool as a surrogate in vitro model for
predicting drug toxicity in patient groups at high risk for drug-induced arrhythmia. The study will use the “cell
village” platform to co-culture 10 different patient-specific iPSC lines simultaneously. We will scale this up by
multiplexing data from 100 different donors to identify cell-type-specific expression quantitative trait loci (eQTL)
using single-cell RNA sequencing (scRNA-seq) and whole genome sequencing (WGS). As a proof-of-principle,
we will also assess inter-individual and intra-individual variability in responses to the chemotherapeutic agent
doxorubicin. Finally, Greenstone Biosciences, Inc is a biotechnology company located at the Stanford Research
Park. Greenstone uses latest advances in clinical genomics, computational biology, and patient-specific iPSCs
to understand pharmacogenomics and to accelerate drug discovery.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Syed Mukhtar Ahmed其他文献
Tackling the challenges of new approach methods for predicting drug effects from model systems.
应对从模型系统预测药物效应的新方法的挑战。
- DOI:
10.1038/d41573-024-00081-9 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Paul D Pang;Syed Mukhtar Ahmed;Masataka Nishiga;Norman L Stockbridge;Joseph C Wu - 通讯作者:
Joseph C Wu
TIRF顕微鏡による内在性exocystのリアルタイムイメージング
使用 TIRF 显微镜对内源性外囊进行实时成像
- DOI:
- 发表时间:
2018 - 期刊:
- 影响因子:0
- 作者:
福田尚代;Syed Mukhtar Ahmed;Ian G. Macara - 通讯作者:
Ian G. Macara
Syed Mukhtar Ahmed的其他文献
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